Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function
| Autor: | Vera-Marie E. Dunlock, Abbey B. Arp, Simar Pal Singh, Stéphanie Charrin, Viet Nguyen, Erik Jansen, Fleur Schaper, Martin Ter Beest, Malou Zuidscherwoude, Sjoerd J. van Deventer, Britt Nakken, Peter Szodoray, Maria C. Demaria, Mark D. Wright, Laia Querol Cano, Eric Rubinstein, Annemiek B. van Spriel |
|---|---|
| Přispěvatelé: | Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Oslo University Hospital [Oslo], University of Oslo (UiO), Monash University [Melbourne], Rubinstein, Eric |
| Rok vydání: | 2022 |
| Předmět: |
nanodomain
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] T-Lymphocytes T cells lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Receptors Antigen T-Cell [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Tetraspanin 25 [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] plasma membrane Lymphocyte Activation General Biochemistry Genetics and Molecular Biology phosphatase Mice All institutes and research themes of the Radboud University Medical Center Cell Movement [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Animals Protein Isoforms CD45 CP: Immunology tetraspanin Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Leukocyte Common Antigens CD53 signaling TCR Signal Transduction |
| Zdroj: | Cell Reports, 39 Cell Reports, 39, 13 Cell Reports Cell Reports, 2022, 39 (13), pp.111006. ⟨10.1016/j.celrep.2022.111006⟩ |
| ISSN: | 2211-1247 |
| Popis: | International audience; T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53-/-) exhibit substantial proliferation defects, and Cd53-/- mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|